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Examining Male Infertility
Susanne Quallich
A
n increasing number of
couples seek evaluation
and treatment for infertility, especially as more
couples delay childbearing in
order to establish their careers. A
male factor alone is the cause of
infertility in up to 20% of infertile couples and a contributing
factor in another 30% to 40% of
all couples presenting for infertility
evaluations
(American
Urological Association [AUA] &
American Society for Reproductive Medicine (ASRM), 2001a;
ASRM, 2004). Problems with
infertility affect approximately 6.1
million people in the United
States, or roughly 10% of the
reproductive-age population. For
these couples, a lack of success
with conception is not just an
inconvenience but rather a disease
of their reproductive system(s).
Understanding the basics of male
infertility is an important part of
providing complete urologic care
to male patients.
There are causes of male infertility that are treatable, either
through medical or surgical management, and causes that can be
corrected, or improved, to the
point where the couple is able to
conceive naturally or to take
advantage of less-costly assisted
Susanne Quallich, APRN, BC, NPC, CUNP, is a Nurse Practitioner,
Division
of
Andrology
and
Microsurgery, Michigan Urology
Center, University of Michigan Health
System, Ann Arbor, MI; and an
Urologic Nursing Editorial Board
Member.
Problems of male infertility can seem like minor issues within the
larger realm of urology. But many male infertility diagnoses can be
successfully treated, allowing the couple to conceive naturally or
with minimal medical assistance. Some patients presenting with male
infertility can have more significant disease. Treatments for male
infertility will continue to progress, and as an increasing number of
couples seek infertility services, the need to provide basic information grows as well.
reproductive technologies.
It is common to recommend
an infertility evaluation in couples
with a history of unprotected
intercourse for at least 12 months
without a pregnancy and with
attempts to time intercourse with
ovulation, although this length of
time can be shortened as the
female partner’s age increases to
over age 35 or if the couple is worried about their fertility status.
This guideline is relevant even if
the couple has previously had
children together. A couple can
present with a history of little difficulty achieving a first pregnancy,
and yet be unsuccessful in establishing a second pregnancy (secondary infertility). There are other
reasons to consider an evaluation,
such as female infertility issues,
including age greater than 35, or a
history of male risk factors for
infertility, such as cryptorchidism
or a history of cancer treatment. A
screening evaluation for the couple should include a reproductive
history and at least two semen
analyses at a laboratory that is
qualified to perform the testing.
Development of Sperm
Males do not begin to produce sperm until puberty, when
testosterone begins to exert its
UROLOGIC NURSING / August 2006 / Volume 26 Number 4
influence on overall male development and growth. Spermatogenesis
is driven by testosterone production
in the Leydig cells of the testes.
Under the influence of luteinizing
hormone (LH) and follicle-stimulating hormone (FSH), which are
released from the anterior pituitary,
the testes begin to produce sperm in
a four-step process of development:
spermatogonia, spermatocyte, spermatid, spermatozoon. This cycle
takes roughly 74 days to complete,
with an additional 12 days for final
maturation as the sperm traverse
the length of the epididymis
(Sigman, Lipshultz, & Howards,
1997). The duration of this cycle
is important, as any changes in
the semen analysis following
medical or surgical intervention
will not be reflected for at least 3
months.
This process is governed by a
negative feedback loop, with
testosterone acting as the primary
negative feedback component
that slows LH and FSH secretion.
Inhibin, released during spermatogenesis, also specifically
inhibits activity or down-regulates FSH. This feedback system
can be overridden by the administration of exogenous testosterone, or medications such as
luteinizing hormone-releasing
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hormone antagonists, both of
which stop the body’s own production of testosterone (and halt
spermatogenesis as well).
History
General history and review of
systems. The general history of a
male patient during an infertility
evaluation begins with the duration of the attempts at pregnancy
or reason for the evaluation (such
as to establish if spermatogenesis
has returned after chemotherapy).
It includes many questions
regarding the reproductive status
of his partner, including her age,
the duration of the couple’s
attempts at pregnancy, if they
have had children or a positive
pregnancy test together, and the
results of any semen analyses
prior to the current encounter.
The history addresses whether or
not either partner has conceived
with another partner, and should
include previous evaluation and
treatment for male or female factor infertility in the past. Not
every male patient is accompanied by his partner, but this information should be collected as
completely as possible.
The male general history
includes a discussion of any
recent (within the last 6 months)
systemic illness, particularly if it
was a febrile illness, and any
recent weight gain or loss. The
patient should be asked if there
are any complaints specific to the
genitourinary (GU) structures.
This may reveal complaints of a
dull ache or fullness to the scrotum, or pain on one side that does
not radiate. The review of systems will specifically include
fevers, colds, sinus infections,
anosmia (loss or impairment of
the sense of smell), peripheral
field visual problems, breast pain
or secretions, and scrotal pain. It
should establish that puberty
started in the early or middle
teens to confirm normal physiologic male development.
The general history includes
any potential exposure to envi-
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ronmental toxins, either through
occupation or hobbies. These
include excessive heat, radiation,
heavy metals, and glycol ethers or
other organic solvents.
Medical history. The evaluation should then proceed to a history of any condition that would
potentially affect erectile function, the testes, or the hormonal
status of the patient (including
such things as cryptorchidism,
epispadias, mumps, orchitis, diabetes, hypothyroidism, varicocele, or pituitary malfunction). It
will also include a review of additional medical conditions for
which the patient is being followed, including any condition
that would require radiotherapy
or chemotherapy. Any history of
treatment for malignancy, regardless of site, should be documented. Diabetes, chronic obstructive
pulmonary disease, sleep apnea,
renal insufficiency, hemachromatosis, and hepatic insufficiency
are known possible contributors to
male
subfertility
(Burrows,
Schrepferman, & Lipshultz,
2002). Infertility in the male can,
in fact, be a hallmark symptom
for other medical conditions in
an apparently healthy adult male.
Surgical history. The surgical
history during the male infertility
visit focuses on any history of GU
surgeries at any point during the
life of the male undergoing evaluation. These include such diverse
procedures such as orchidopexy;
Y-V plasty to the bladder neck;
inguinal hernia repair as infant,
small child, or adult; epispadias
or hypospadias repair; prostate
surgery; bladder reconstructions;
bladder surgeries; or testicular
surgeries. The surgical history
should ask about procedures
which impair retroperitoneal
sympathetic nerve function, such
as retroperitoneal lymph node
dissection (RPLND). The patient
should be asked specifically
about previous treatment for testicular or GU malignancies, either
with surgery or radiation. The
patient should be asked specifi-
cally if there is a history of a
vasectomy.
Sexual history. The history
should include the overall pattern of sexual activity during the
period of time the couple has
been trying to conceive, specifically in relation to ovulation.
This includes questions regarding the use of ovulation-predictor kits or ovulation-promoting
medications such as clomiphene
citrate, a nonsteroidal anti-estrogenic. The optimal window for
pregnancy occurs in the 6 days
before ovulation, with day 6
being the actual day of ovulation
(Wilcox, Weinberg, & Baird,
1995). Simply adjusting the timing of intercourse can result in a
significantly increased chance
for pregnancy.
Both partners should be
asked about a history of sexually
transmitted infections. Each
patient should be queried regarding erectile function, ejaculation,
and libido; these issues can be
superimposed onto fertility concerns. Erectile difficulties may be
accompanied by a history of
declining erectile function, usually insidious and progressive, and
may span the course of several
years (as is a common scenario
with diabetic patients). Alternatively, the patient may provide
a history of relatively rapid or
recent onset of a decline to erectile function, such as may be associated with the history of recently
starting new medication or the
stress of the fertility evaluation.
The history should include several points specific to the patient’s
sexual functioning: the precise
nature of the dysfunction (for
example, whether the problem is
attaining or sustaining an erection, insufficient rigidity, difficulty with penetration); the presence
or absence of nocturnal and
morning erections and their quality; and any treatments (pharmacologic and nonpharmacologic)
that the patient has tried.
If the patient complains of
low libido, he may also describe
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moodiness, loss of interest in his
usual activities, a decline in erectile function, fatigue, and even
complaints of diminished muscle
bulk. It should be established if
these complaints are new or longstanding.
If there are issues with ejaculation, the patient may have complaints of cloudy urine after ejaculation, decreased volume of
ejaculate, hematospermia, difficulty with bowel movements,
anejaculation, oligospermia (low
sperm count), or azoospermia (no
sperm in ejaculate) with a lowvolume ejaculate on semen analysis. The patient may have complaints of pain on ejaculation,
usually of relatively recent onset,
and it may localize to a specific
scrotal structure. These complaints can be the result of a variety of surgical procedures, progressive neurologic disease, or
pre-existing treatment with certain antidepressants (see the article, “Premature Ejaculation” elsewhere in this issue for a more
detailed description of ejaculation issues).
The couple must also be asked
about the used of lubricants: saliva,
K-Y® jelly, surgilube, and hand
lotions are known to impair sperm
motility (Burrows et al., 2002).
Medication history. A careful
medication history is a mandatory component of the initial evaluation of male-factor infertility.
Prescription drugs can affect
sperm count, motility, and morphology, and the dose and duration of use should be documented. Common antibiotics can temporarily contribute to a decline in
the semen analysis quality; calcium channel blockers and
spironolactone can contribute to
a decreased fertilization capacity
and a decline in spermatogenesis
respectively (Brugh, Matschke, &
Lipshultz, 2003) (see Table 1).
Anabolic steroid use can result in
a profound decline in sperm
counts that may not recover with
the cessation of the exogenous
steroid, leaving the patient
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Table 1.
Common Medications with an Effect on Sperm Function
Medication
Effect
Spironolactone
Decreases spermatogenesis
Calcium channel blockers
Decreases fertilization capacity
Anti-androgens
Decreases spermatogenesis
Nitrofurantoin (high doses)
Decreases spermatogenesis
Cimetidine
Decreases spermatogenesis
Cyclosporine
Decreases spermatogenesis
Colchicine
Decreases fertilization capacity
Erythromycin
Decreases sperm density/motility
Source: Adapted from Brugh, Matschke, & Lipshultz, 2003.
azoospermic or with persistently
decreased counts. The patient
must also be asked about the
ingestion of nutraceuticals and
other over-the counter medications, certain steroid hormones,
or other harmful substances that
may contribute to semen analysis
derangements as well.
Social history. Cigarette
smoking, excessive alcohol consumption, and consistent marijuana use are all known to be
gonadotoxins (Burrows et al.,
2002). A careful history of the use
of these agents and other illicit
drug use must be part of the complete male infertility evaluation.
Cigarette smoking has been
implicated as leading to changes
in morphology, sperm production, and motility while chronic
alcohol use contributes to feminization, erectile dysfunction, and
hypogonadism (Nudell, Monoski
& Lipshultz, 2002). Marijuana use
can decrease sperm morphology
over time (Nudell et al., 2002).
Simply eliminating these agents
can improve semen parameters in
the absence of other physical findings.
Patients should be asked
about recreational activities, as
some activities, such as long-distance cycling, may put pressure
on the perineal area and may
UROLOGIC NURSING / August 2006 / Volume 26 Number 4
result in possible impairment to
erectile function.
Family history. The family
history should include a discussion of testicular or other GU
malignancies and specifically any
cancer history, prostate or bladder problems in other family
members (including female relatives with bladder conditions). It
is helpful to include a history of
maternal medication/drug use
while pregnant with patient, if
this information is known. The
patient should be queried regarding siblings or extended family
members who may have had fertility problems or diagnoses that
are genetic in nature (such as cystic fibrosis).
Female partner history. The
history of the patient’s partner
should include details of any previous pregnancies (including
miscarriages or elective terminations), menstrual cycle length,
whether she is undergoing evaluation for fertility issues, and any
medical or surgical management
that has been necessary. It is also
helpful to include comments
regarding the expected next step
in her management (if known) if
the male evaluation is negative.
Physical Examination
If this is a complaint in a man
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with no other recognized medical
conditions, a full physical examination is necessary. Examination
of the male patient is best done in
a warm room, in an attempt to
avoid any exaggeration of the cremaster reflex (see Table 2). The
examination should focus pri-
marily on the genitalia (see Table
3), with consideration for the
overall body habitus. For a
detailed discussion of the complete male physical examination,
refer to the physical assessment
article that appears elsewhere in
this issue. The structures that are
Table 2.
Special Maneuvers for the Male Infertility Examination
Maneuver
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Description
Cremasteric
reflex
Brushing or touching the skin of the scrotum in a downward direction will result in the prompt elevation of the
testicle on the same side. This reaction can be aggravated
by a cool room; the reflex may be engaged prior to any
contact with examiner.
Valsalva
maneuver to
evaluate for
varicocele
Performed with patient standing, and in warm room; having
patient perform Valsalva will reverse flow into the pampiniform plexus and result in palpable distention of the vessels
(“bag of worms” if varicocele of sufficient size).
Source: Quallich, 2005.
evaluated include the penis, scrotum, testes, epididymis, spermatic cord and vas deferens, prostate,
seminal vesicles, and Cowper’s
gland; however, not all are easily
palpated.
The patient should be examined for age-appropriate development of male secondary sex characteristics, gynecomastia, or hirsutism. He should be evaluated
for lesions or scarring to the
abdomen or groin (as patients
may inadvertently neglect to
mention surgery that happened
in their remote past), any discoloration to the scrotum, asymmetry of the testicles, and the location and size of the opening of the
penile meatus. Physical examination could reveal regression of
secondary sexual characteristics
such as hair loss and possible loss
of muscle bulk. Patients using
Table 3.
Physical Findings and Their Relationship to Male Infertility
Visible Male
Reproductive
Structure
Normal Findings on
Inspection/Palpation
Abnormalities Relevant to
Infertility Evaluation
Penis
Soft and pliable along length of shaft.
Meatus midline, central to glans.
Foreskin should retract and draw forward easily.
Meatus not midline or central to glans –
hypospadias, epispadias.
Scrotum
Sac of skin partially covered with hair.
Unilateral, uncomfortable swelling of the
scrotum – varicocele.
Testes
Two testes, freely movable within scrotum;
should be nontender.
Palpate between thumb and 1st two fingers of
the hand.
Firm, smooth, rubbery consistency.
Average 6 cm x 4 cm in size, symmetrical.
Right testicle may be slightly anterior to left.
Separate from epididymis.
Mass associated with testicle – tumor,
spermatocele.
Solitary testis – maldescent of testicle or
previous surgical removal.
Small, soft testicle(s) – Klinefelter’s syndrome, history of infection, late orchidopexy, atrophy due to long-standing
varicocele.
Epididymis
Soft ridge of tissue longitudinally posterior to
testicle.
Separate from testicle.
Cystic or nodular – spermatocele, previous infection, history of vasectomy.
Large and/or fluctuant – spermatocele.
Localized pain – epididymitis.
Vas deferens and
spermatic cord
Soft, rubbery consistency.
Trace vas deferens from epididymis to inguinal
canal.
Smooth along entire length.
Absence of vas bilaterally or unilaterally
– cystic fibrosis/CF variant.
Sperm granuloma – s/p vasectomy.
Congested veins unilaterally or bilaterally
– varicocele.
Beading/nodularity of the cord – possible
obstruction of epididymis.
Source: Adapted from Quallich, 2005.
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anabolic steroids may also have
skeletal muscle hypertrophy,
acne, gynecomastia, and striae;
there may be some noticeable testicular atrophy on examination.
Palpation is the most important component of the physical
examination when assessing for
male factor infertility. Because
the tone of the tunica dartos muscle will determine the size of the
scrotum, the examination should
be performed in a warm room
whenever possible. In a cool
environment the tunica dartos
muscle will cause the scrotum to
contract. The scrotum must be
carefully and thoroughly palpated, and the presence of all scrotal
structures should be confirmed,
along with their size and consistency. Masses may arise from the
surface of the testicle, adjacent to
or separate from the testes. There
may be evidence of epididymal
induration on physical examination. The patient may have a testicle that is palpable in the
inguinal canal and can be tender
on examination, that cannot be
manipulated down into the scrotum, or that cannot be palpated at
all. Physical examination may
show complete absence of the vas
deferens unilaterally or bilaterally, or a palpable gap in the vas
deferens. The complete physical
examination should also include
a digital rectal examination when
there are ejaculatory complaints.
A varicocele can be exaggerated during physical examination
by asking the patient to perform
the Valsalva maneuver while
standing; any distention of the
pampiniform plexus should disappear when the patient lies
down. If the varicocele is bulky
enough, there may be resulting
scrotal swelling that is noticeable
to the patient, along with a bluish
discoloration beneath the scrotal
skin. A long-standing varicocele
may cause testicular atrophy. If
the varicocele is large, it may be
visible during inspection (“bag of
worms”).
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Table 4.
Semen Parameters
Semen Parameters
Normal Values
Morphology (strict criteria)
> 15% normal forms
Motility
> 50%
Sperm concentration
> 20 million
Volume
2.0 ml - 5.0 ml
Source: Adapted from Rowe, Comhaire, Hargreave, & Mahmoud, 2000.
Semen Analysis and
Laboratory Evaluation
The semen analysis yields a
tremendous amount of information as to the potential causes of
male infertility. The primary values that are evaluated are the volume of the ejaculate, sperm motility, total sperm count, and sperm
morphology (shape) (see Table 4).
Patients should receive notification in advance that they will
need to provide a semen sample
after a period of abstinence of 2 to
5 days. This sample is collected
through masturbation, and must
be collected into a container that
is not toxic to sperm, or by using a
special condom designed for
semen collection (latex condoms
alter sperm viability, especially if
they are lubricated). Patients
should be discouraged from
attempting to collect a sample
through intercourse as coitus
interruptus is not a recommended, or reliable, means for sample
collection (AUA & ASRM, 2001b).
The ideal circumstances for specimen collection are in close proximity to the laboratory to prevent
any delay in processing. If the
sample is collected at home it
should arrive to the lab within 60
minutes to ensure the accuracy of
the results.
When determining a course
of treatment, it is common to
require serial analyses to avoid
any spurious results, ideally with
the same period of abstinence
each time. For instance, patients
could be scheduled for three
UROLOGIC NURSING / August 2006 / Volume 26 Number 4
specimens, with 3 days abstinence, a minimum of 3 weeks
apart. It is common for patients to
repeat their semen analysis every
3 months after starting any treatment, due to the length of time it
takes sperm to mature. The
results of the semen analysis can
indicate any additional testing
that might be useful.
There are several additional
tests that can be performed on a
semen sample, including a sperm
penetration assay, peroxidase
staining, direct immunobead testing, and computer-aided semen
analysis. The clinical usefulness
of specialized sperm testing
remains controversial, however.
An endocrine evaluation can
yield a great deal of information
(see Table 5), and may be ordered
if there is any suspicion of
endocrinopathy or evidence of
oligospermia. This will include
total testosterone, free testosterone, LH, FSH, and prolactin
levels; estradiol level may be
included if the patient has a high
body mass index.
If the semen analysis shows
severe oligospermia or azoospermia and/or the physical examination yields abnormalities as far as
testicular size or the male’s overall physical development, then
karyotype analysis and Y-chromosome microdeletion testing
are also indicated.
Potentially Reversible Causes
Of Male Infertility
Varicocele. A varicocele is a
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Table 5.
Endocrine Abnormalities Seen with Male Infertility
Condition
Testosterone level
LH level
Abnormal spermatogenesis
Normal
Normal
Anabolic steroid use
Elevated or low
Decreased
(depends on specific
chemical)
FSH Level
Prolactin
Elevated or normal Normal
Decreased
Normal
Hypogonadotropic hypogonadism Decreased
Decreased
Decreased
Normal
Normal spermatogenesis
Normal
Normal
Normal
Normal
Partial androgen resistence
Elevated
Elevated
Normal
Normal
Testicular failure
Decreased or normal Elevated
Elevated
Normal
palpable or visible dilation of the
vessels of the pampiniform
plexus in the scrotum. It is the
reflux of venous blood from the
internal spermatic vein which
dilates the pampiniform plexus
and results in a varicocele. It is
estimated that varicoceles may be
present in 15% of the male population, and this number increases
to 40% in men presenting for an
infertility evaluation (AUA &
ASRM, 2001c). Varicoceles are
more common on the left, possibly due to the greater distance the
internal spermatic vein must traverse to the left renal vein when
compared with the distance on
the right. If a varicocele is
painful, there may be a history of
a dull ache, fullness, pain that
does not radiate, or pulling to the
affected side of the scrotum after
prolonged standing, exertion, or
sitting. Pain from a varicocele is
rare after prolonged recumbency
or sleeping.
A varicocele might be suspected in the male with
decreased semen parameters, as
varicoceles represent a common
cause of secondary male infertility. The etiology of varicoceles
remains unclear, and there are no
specific risk factors. The mechanism by which varicoceles alter
the semen analysis is also uncertain, and may be the result of temperature elevation, venous congestion, or testicular hormone
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changes. It is unusual for males to
exhibit a varicocele prior to adolescence, and the majority of
varicoceles are asymptomatic,
causing neither pain nor semen
analysis changes. Adult males
with a varicocele and some
abnormalities of their semen
parameters may benefit from
treatment for the varicocele as a
way to protect their future fertility and prevent any potential for
future decline to their semen
parameters (Chehval & Purcell,
1992).
A scrotal ultrasound is not
necessary to diagnose a varicocele, but it will confirm the presence of a varicocele and eliminate
other testicular or scrotal pathology. However, only those varicoceles palpable on physical examination have been documented as
contributing to male infertility
(AUA & ASRM, 2001c).
Treatment of a varicocele is
possible either through surgical
repair or percutaneous embolization. Surgical repair can be
achieved with a variety of
approaches, including microsurgical, inguinal, or subinguinal.
Neither embolization nor surgery
has been clearly shown to
improve fertility (AUA & ASRM,
2001c). Any offered surgical correction will be secondary to the
individual surgeon’s experience,
while embolization requires interventional radiology. Surgical
treatment has a high success rate
(AUA & ASRM, 2001c). Both
surgery and embolization have
short recovery periods. The primary risks are infection, varicocele recurrence, and failure of the
semen analysis to improve after
the procedure. For those patients
who do not show improvement
or show only modest improvement over the course of a year,
and in whom the varicocele has
not recurred, intrauterine insemination (IUI) or in vitro fertilization (IVF) may be advised,
depending on the total sperm
count.
Ejaculatory and Sexual
Dysfunction
A secondary goal of the infertility evaluation is to identify any
underlying health conditions that
may be contributing to difficulties with conception. This could
include any conditions that
would contribute to problems
with ejaculation, such as undiagnosed diabetes, or problems with
erection, such as might be caused
by a significant smoking history,
severe hypercholesterolemia, or
hypogonadism. A full discussion
of the diagnosis and treatment of
erectile dysfunction (ED) is
beyond the scope of this article;
however, it is not uncommon for
men to report some stress-related
ED during the course of the infertility evaluation and treatment.
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These patients may benefit from a
prescription for a PDE-5 inhibitor.
Alprostadil (Muse®) is not recommended since its potential effect
on the ejaculate is not known.
Patients who complain of difficulty with ejaculation and climax may be taking psychotherapeutic
agents
that
block
dopamine production and consequently blunt the hypothalamicpituitary axis and possibly
decrease libido. Other psychotherapeutic agents can decrease
vasodilation and decrease the quality of erections. Tricyclic antidepressants, selective-serotonin reuptake inhibitors, and monoamine
oxidase inhibitors can lead to ED,
anejaculation, and decreased
libido. These patients can have
their regimen changed, or may be
offered other means of medically
managing their complaints, such as
a PDE-5 inhibitor.
Endocrinopathy. Hypogonadism represents the only cause of
male infertility that can successfully be treated with hormone therapy,
although the response is largely
dependent on the length of time
and causes of the hypogonadism.
Hypogonadism is failure of the
testes to produce normal levels of
testosterone and/or sperm. Primary causes of hypogonadism are
commonly due to testicular failure,
while secondary causes are due to
pituitary or hypothalamic causes,
and combined hypogonadism is
due to the combinations of the
decreased pulsatility of the pituitary gonadotropins coupled with
the decreased response of the testicular Leydig cells. Hypogonadism is more common in aging
males who have passed through
their reproductive stage.
Reversible endocrinopathies
that directly contribute to male
infertility are unusual (Kolettis,
2003). In the adult male, hypogonadism manifests with changes
in sexual function, behavior,
muscle mass, and some loss of
secondary sexual characteristics.
The patient may also report mood
and behavioral symptoms (de-
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pression, irritability, loss of motivation) in addition to complaints
of lethargy or loss of energy.
Physical
examination
may
demonstrate some regression of
secondary sexual characteristics
such as hair loss and possible loss
of muscle bulk. There is no
change to penis or prostate size,
but the testes may be softer in
consistency and smaller than
might be expected from the
patient’s chronologic age.
Obesity can lead to the aromatization of testosterone in fatty
tissue to estradiol, leaving less
testosterone available for maintenance and virilization functions.
This will lead to a decline in
sperm production, as the testes
no longer receive an adequate
hormonal signal to produce
sperm. As a result of lowered
testosterone, a clinically obese
male may demonstrate evidence
of feminization (such as gynecomastia) or regression of secondary
male sexual characteristics on
physical examination. Testosterone and free testosterone levels, along with estradiol, LH, and
FSH levels will aid in determining the degree to which obesity
may have upset the patient’s hormonal balance and contributed to
alterations to the semen analysis.
The most definitive treatment is
weight loss, but some patients may
also respond well to treatment with
clomiphene citrate, a synthetic
nonsteroidal anti-estrogen.
All forms of hypogonadism
can be confirmed by checking a
testosterone level; morning values are preferred to afternoon
blood samples because testosterone is secreted in the morning.
This should include total testosterone, free testosterone, LH, and
FSH. Estradiol should be obtained if the patient has a higher
body mass index. Prolactin and a
thyroid profile can also be useful
in diagnosing secondary causes
in selected cases.
Men who are diagnosed with
hypogonadotropic hypogonadism
(decreased testosterone, decreased
UROLOGIC NURSING / August 2006 / Volume 26 Number 4
LH, decreased FSH) can also benefit from treatment with exogenous hormones to stimulate their
system into a more normal profile. Their prospects for recovery
of spermatogenesis are modest;
even with treatment it may be a
year or more before sperm production returns. The most profound cases of this are caused by
hypothalamic disorders such as
Kallman’s syndrome. Men diagnosed with a form of hypogonadotropic hypogonadism may
still sire genetic offspring, via testicular aspiration and IVF and
intracytoplasmic sperm injection
(ICSI).
Obstructive
azoospermia.
Patients who have previously had
vasectomies suffer from obstructive azoospermia. These patients
are usually otherwise healthy,
and have normal GU examinations, with the exception of
sperm granulomas as a result of
the vasectomy, and varying
degrees of induration and/or tenderness to their epididymis.
These patients can be offered a
vasectomy reversal as treatment
for their infertility, and may be
candidates for a vasovasotomy or
vasoepididymostomy depending
on their physical examination
(AUA & ASRM, 2001b). The
offered surgical approach will be
based on the individual surgeon’s
experience. Vasectomy reversals
may become less successful as
the time after the vasectomy
increases. A microsurgical vasectomy reversal remains the most
cost-effective option for fertility
restoration after a vasectomy
(Pavlovich & Schlegel, 1997).
A minority of patients presenting for a male infertility evaluation may have suffered an
inadvertent vasectomy during
surgery for another condition,
such as a inguinal hernia repair as
a child or adult. In some cases
these patients can be successfully
reconstructed.
Ejaculatory duct obstruction.
Ejaculatory duct obstruction describes a condition in which one, or
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both, of the ducts leading from the
seminal vesicles into the prostate
become(s) partially or completely
blocked. This results in only prostatic fluids contributing to the
ejaculate volume. As a result the
semen analysis will show
decreased volume, increased acidity, possible hematospermia, possible oligospermia, or azoospermia.
The patient may provide a history
of pain immediately following ejaculation. Digital rectal examination
may show some tenderness to the
prostate and/or epididymis, and
possible distended seminal vesicles, but the diagnosis is more commonly made after a transrectal
ultrasound. Treatment involves the
transurethral resection of the ejaculatory ducts.
Chemotherapeutic agents.
Men who have been treated with
chemotherapeutic agents have
varying chances of recovering
spermatogenesis, depending on
the specific agents involved.
Damage is done directly to the
germinal epithelium and Sertoli
cells that support spermatogenesis. The most gonadotoxic agents
are alkylating agents, antimetabolites, and vinca alkaloids (Nudell
et al., 2002). Agents such as
methotrexate, cisplatin, and 6mercaptopurine offer better
chances of sperm recovery
(Nudell et al., 2002), but offering
the opportunity to cryopreserve
sperm prior to initiation of treatment should be considered whenever possible. Spermatogenesis
can recover during the 2 to 4 years
after the cessation of treatment;
progress toward recovery can be
monitored with yearly semen
samples.
Male Infertility and Medical
Management
Medical management of male
infertility occurs when a specific
contributing factor that is potentially amenable to attempts at
medical treatment is identified.
This routinely includes the recommendation to remove any
environmental toxins, such as
284
Page 284
Table 6.
Discussion of Clomiphene Citrate
(Selective Estrogen Receptor Modulator)
Male
Female
Action
Functions at level of pituitary: Functions at level of pituitary:
causes increased FSH secretion causes increased FSH secretion
Result
Increased testosterone pro- Stimulates ovulation
duction, likely increased sperm
production, increased sperm
count, and concentration
Potential
adverse
effects
Dizziness
Gynecomastia
Headache
Lightheadedness
Mental depression
Vision problems (rare)
smoking cessation, cessation of
recreational drug use, and cessation of alcohol intake. Medical
management is often related to
addressing some endocrine
abnormality; in the case of a specific hormone deficiency, administration of the hormone, or a substance that promotes its production, can restore the patient to
normal hormone levels. After a
period of time, 6, 9, 12 months or
more, there can be improvements
in overall semen parameters
either to normal ranges or such
that the couple becomes a candidate for low-tech interventions.
This is true for all attempts at
hormone replacement except for
testosterone. The patient who is
given any form of testosterone
replacement will suffer a progressive decline in the function of the
testicles, as the exogenous testosterone is a powerful inhibitor of
the feedback loop that governs
spermatogenesis and testicular
testosterone production. To boost
testosterone levels in the subfertile male, clomiphene citrate
(Clomid®), a synthetic nonsteroidal anti-estrogen is given,
commonly at 25 mg daily. In men,
it blocks feedback inhibition and
so increases FSH and LH, thus
increasing testosterone and
sperm production. In part,
Abdominal discomfort
Abnormal uterine bleeding
Headache
Ovarian hyperstimulation
syndrome
Vasomotor flushes
Visual symptoms
because of its estrogenic effects,
there is the potential for alterations in libido, gynecomastia,
weight gain, and headache (see
Table 6). There have been a variety of uncontrolled studies as to
the effectiveness of clomiphene
citrate in treating male subfertility, but when the outcome is measured as an increase in pregnancy
rate, clomiphene citrate fares little better than placebo (Sokol,
Steiner, Bustillo, Petersen, &
Swerdloff, 1988). It will not have
an effect on the male who has a
normal testosterone level and a
decreased semen analysis.
If there is retrograde or lowvolume ejaculation, a trial of sympathomimetics can be useful. The
goal of this therapy is to convert
the retrograde ejaculation to antegrade or partially antegrade ejaculation; a variety of medications
have been used, with varying
degrees of success (Schuster &
Ohl, 2002). This approach is
more successful with patients
who suffer a progressive decline
in their ejaculatory function, such
as that seen with neurologic disease, than with the abrupt onset
seen as a result of a variety of
surgeries, such as radical retropubic prostatectomy.
Use of the supplement L-carnitine, either by itself or in a mix-
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ture of additional substances, has
been proposed as a supplement
that can improve overall sperm
motility and the total sperm
count, and enabling a patient to
avoid invasive procedures such
as varicocele repair or testicular
biopsy. However, its use remains
somewhat unfounded. Although
carnitine serves a role in the maturation of sperm, there have been
no prospective, randomized, double-blind, placebo-controlled trials to evaluate this supplement’s
utility in improving male-factor
infertility (Siddiq & Sigman,
2002).
Generally, attempts at medical treatments for male infertility
have been limited by poorly
designed research studies, and by
wide variations in dosage and
duration of therapy, lack of a
placebo-control arm, and a failure
to control for the variation seen in
semen quality with time.
Irreversible Causes of Male
Infertility
Klinefelter’s syndrome. Klinefelter’s syndrome is the most
common abnormality of sexual
differentiation, and occurs in
approximately 1 in 500 live
births. It is one of the most common causes of primary hypogonadism, and is the most common
sex chromosome abnormality
seen in infertile men. Patients
will present with a typical triad of
small, firm testes; gynecomastia;
and elevated urine gonadotropins. Variants of Klinefelter’s
may also result in increased
height, diabetes mellitus, obesity,
and decreased intelligence. The
infertility evaluation may be the
first time the patient has a complete physical examination as an
adult.
During the history, patients
may describe the delayed completion of puberty and delayed
virilization. There are usually few
physical complaints associated
with Klinefelter’s syndrome.
There will be a lack of development of secondary sexual charac-
Page 285
teristics on physical examination
(atrophic [< 2.0 cm] testes, small
phallus, diminished body hair,
diminished muscle bulk), and a
feminine, or truncal, rather than
male, fat distribution that often
includes gynecomastia. Patients
may be tall, due to a delay in the
fusion of the epiphyseal plates in
the long bones.
Clinical suspicion after the
physical examination will usually lead to a karyotype analysis,
which will show 47, XXY or a
mosaic pattern such as 46, XY/47,
XXY, indicating a diagnosis of
Klinefelter’s syndrome. Serum
hormone studies will demonstrate a decreased or normal
testosterone, decreased free
testosterone, elevated estradiol,
normal or elevated LH, and elevated FSH.
Treatment for infertility in
the patient with Klinefelter’s can
take a variety of forms (see Table
7). It is only recently, with the
advent of the microTESE (microsurgical testicular extraction) procedure, that patients diagnosed
with Klinefelter’s syndrome were
given the potential to father
genetic offspring via microTESE
and ICSI (intracytoplasmic sperm
injection).
Congenital bilateral absence
of the vas deferens. Congenital
bilateral absence of the vas deferens is a genetic abnormality that
is seen with cystic fibrosis (CF)
and its multiple variants. If not
previously diagnosed with cystic
fibrosis, the patient may have one
of the less-severe CF mutations,
and report a history of chronic
bronchitis that may have required
hospitalization, recurrent respiratory infections as a child and adolescent, asthma or an asthma-like
condition, or even have no symptoms at all (most common). There
are usually no other physical
complaints; but there may be a
family history of infertility or persistent respiratory illnesses.
Males with CF frequently
demonstrate malformation of the
epididymis. The vas deferens,
UROLOGIC NURSING / August 2006 / Volume 26 Number 4
seminal vesicles, and ejaculatory
ducts are generally atrophic or
absent. Physical examination
may show complete absence of
the vas deferens unilaterally or
bilaterally, or a palpable gap in
the vas deferens. Testosterone
levels in these patients will be
normal. Spermatogenesis is usually normal as well, and so testes
size and consistency are normal,
with the patient describing normal libido and demonstrating
appropriate secondary sexual
characteristics. It is possible that
the patient may have a much
more rare unilateral absence of
the vas deferens, which is usually
associated with Wolffian duct
abnormalities and renal malformations.
The physical examination
and history are sufficient to confirm a suspicion of CF; the patient
will be sent for karyotype analysis and CF testing. The couple
will be sent to a genetics clinic for
additional counseling and testing. Males with CF have the
option to sire genetic offspring
via testicular aspiration and IVF.
Anejaculation after a spinal
cord injury or surgery. Approximately 80% of spinal cord
injured (SCI) men will demonstrate some preservation of their
erectile function (Schuster & Ohl,
2002). Men with a T9 level injury
or above can have reflex erections
that do not persist long enough or
are reliable for sexual activity. In
men who have suffered lower
motor neuron injuries (below T9),
erectile activity is absent.
Ejaculatory function in men
with SCI is a separate challenge.
Only 5% to 15% of men will have
any evidence of ejaculation after
their injury (Biering-Sørensen &
Sønksen, 2001) and this represents a major aspect contributing
to infertility. This is complicated
further by a significant decline in
overall sperm quality. Sperm
obtained from men who are
unable to ejaculate demonstrate a
variety of abnormalities that
include significantly decreased
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Page 286
Table 7.
Examples of Treatment Options for Male Infertility Diagnoses
Diagnosed Condition
Treatment Option A
Treatment Option B
Treatment Option C
Antisperm antibodies
IUI
IVF + ICSI
Donor insemination + IUI
Cystic fibrosis
Testicular sperm extraction
with IVF
Donor insemination + IUI
Adoption
Diabetes with
anejaculation
Trial of sympathomimetic
to promote antegrade
ejaculation
Testicular sperm extraction
with IVF
Donor insemination + IUI
Failed vasectomy reversal
Testicular sperm
extraction with IVF
Donor insemination + IUI
Adoption
Hypergonadotropic
hypogonadism
Possible hormone
replacement
Testicular sperm extraction
with IVF
Donor insemination + IUI;
Adoption
Idiopathic male infertility
IUI +/- donor insemination
(depends on count)
IVF +/- ICSI
(depends on count)
Adoption
Klinefelter’s syndrome
MicroTESE and IVF + ICSI
Donor insemination + IUI
Adoption
Persistent low sperm
count after medical or
surgical treatment
IUI
Donor insemination + IUI
IVF
Retrograde ejaculation
Trial of sympathomimetic
to promote antegrade
ejaculation
IUI
Testicular sperm extraction
with IVF
Varicocele
Varicocele repair
IUI
IVF
IUI: Intrauterine insemination
IVF: In vitro fertilization
ICSI: Intracytoplasmic sperm injection
motility and viability, decreased
ability to penetrate cervical
mucus, and decreased fertilizing
capability. Only 5% of men with
SCI will be able to initiate a pregnancy without some degree of
medical intervention (Schuster &
Ohl, 2002).
Surgical procedures in the
pelvis or retroperiteneum can result
in neurogenic impairment of the
ejaculatory process by damaging
peripheral nerves. This can manifest as an incompetent bladder neck
and retrograde ejaculation, or total
anejaculation. Men with testis cancer, in particular, are at risk for this
type of injury with a RPLND. Men
who suffer from surgically induced
anejaculation will experience
decreases to their semen quality
similar to that of men with SCI.
286
Anejaculatory men can still
father their own children; both
penile vibratory stimulation
(PVS) or electroejaculation (EEJ)
are successful options for specific
groups of patients and allows the
possibility for IUI (see Table 8).
Alternatively, anejaculatory men
have the option to proceed with
testes aspiration and IVF.
Antisperm antibodies (immunologic infertility). Some men
will demonstrate antisperm antibodies that are associated with
their sperm. These can be antibodies that are attached to the
head, tail, or all parts of the
sperm, and their presence
inhibits the fertilizing ability of
the sperm. It is unclear precisely
why these antibodies form, but it
can be the result of vasectomy
and reversal, testis injury or
infection, or cancer; it can also be
idiopathic. Past attempts at treatment of this condition with such
medications as corticosteroids
have met with little success.
These particular patients can be
treated with IUI (low success) or
IVF with ICSI.
Other genetic causes. There are
other less-commonly seen genetic
causes of male infertility that
include conditions such as
Kallman’s syndrome, Y-chromosome microdeletions, various neuromuscular conditions, immotile
cilia syndromes, and Kartagener’s
syndrome. Depending on sperm
counts, these patients can be
offered sperm aspiration with IVF
or IVF and ICSI.
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Page 287
Table 8.
Methods of Sperm Retrieval
Method
Indications
Procedure
Assisted
Reproduction
Options
Penile vibratory
stimulation (PVS) or
electroejaculation (EEJ)
Anejaculation (inability to
ejaculate)
Collected in treatment room in clinic;
application of a vibrator to the penis
(PVS) or probe is inserted into the rectum, and a current is applied, producing erection and ejaculation (EEJ)
IUI
IVF
IVF with ICSI
Retrograde semen
collection
Retrograde ejaculation
Collected in treatment room in clinic or IUI
assisted reproductive technologies (ART) IVF
lab; can also be collected after PVS or EEJ
Epididymal sperm
extraction
Azoospermia; obstructive
azoospermia; absence of
vas deferens
Done in clinic treatment room under
local anesthesia or operating room with
general anesthesia
IVF
IVF with ICSI
Testicular sperm extraction
Azoospermia; obstructive Done in clinic treatment room under
azoospermia; cystic fibrosis local anesthesia or operating room with
general anesthesia
IVF
IVF with ICSI
Testes biopsy
Azoospermia – to
diagnose normal or
abnormal sperm
development; also to
retrieve sperm
Done in clinic treatment room under
local anesthesia or operating room with
general anesthesia
IVF
IVF with ICSI
Microsurgical testicular
sperm extraction
(MicroTESE)
Microsurgical method for
obtaining sperm from a
male who does not have
sperm in his ejaculate
(azoospermia) with severe
production problems
Surgical procedure with local or general anesthesia
IVF with ICSI
Azoospermia: Lack of sperm in the ejaculate
IUI: Intrauterine insemination
IVF: In vitro fertilization
ICSI: Intracytoplasmic sperm injection
Fertility Preservation
The future of infertility treatment continues to evolve. This is
partly a response to changes in
technology as a whole, but is also
inspired but the increasing survival rates of cancers that affect
young people during their reproductive years and the trend for
couples to delay pregnancy.
There are currently available
options for preservation of fertility for men, primarily sperm cryopreservation; this can be a reasonable option for men planning
to undergo chemotherapy or radi-
ation treatment and can serve as a
“backup” in the event that spermatogenesis does not rebound
after treatment. But it is also an
option for those at risk for exposure to toxins or even those being
deployed in the military. The
future may see options for the
storage of testicular tissue, autologous spermatogonial stem cell
transplantation, or gene therapies
to treat genetic causes of male
infertility.
Conclusions
The discussion of treatments
UROLOGIC NURSING / August 2006 / Volume 26 Number 4
for a variety of male infertility
diagnoses requires a basic understanding of male GU anatomy and
function, as well as understanding of the hormonal processes
that control spermatogenesis. The
male infertility evaluation often
represents the first time an otherwise healthy male is faced with
the concept that he is somehow
“not normal.” Not only can this
be an affront to his masculinity,
but depending on the larger religious and/or cultural context,
failure to have children can
impact his standing in his com-
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munity. This can be heightened
by the fact that the outcome is not
always predictable, even with the
use of assisted reproductive technologies. As technologies continue to progress, there will be new
options that become available to
couples whose only options currently are donor insemination or
adoption. •
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EOE
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CE test located on page 289.
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